The use of genetically engineered mice has grown exponentially. Transgenic and genetically deficient mice are now widely used and extremely valuable for the study of the mechanisms of diabetes, endocrine disorders, obesity, and microvascular and macrovascular complications of diabetes as well as elucidating the roles of individual genes in normal physiology, development, and endocrine function. In fact, the genetic manipulation of mice is used in virtually every field of biomedical investigation. It is arguably the most potent tool available to dissect gene function in physiology and pathophysiology. However, because of the prohibitive costs and the technical sophistication required to establish these procedures within individual laboratories, it is essential to support these technologies as a core facility. This requires an efficient and cost-effective common facility that enables individual investigators to have both transgenic mice expressing genes of interest and mice carrying gene disruptions or substitutions created for them. The techniques available from this Core place these potent tools for analysis in the hands of all of our investigators. When used in combination with the other modern techniques supplied by the Center's Mouse Phenotyping, Transcriptional Genomics, and Biochemistry and Molecular Assay Core Core facilities, it gives our investigators unlimited opportunities to examine these processes from several perspectives simultaneously. Our current facility has an established track record of enabling the creation of both transgenic mice and knockout mouse strains for multiple UCSD laboratories. The availability of this Core facility to the entire DERC membership will greatly facilitate the research of the entire diabetes/endocrinology community in Southern California. Without such a centralized resource, most laboratories would not be in a position to utilize these powerful models, severely limiting the research and granting opportunities for our diabetes community. The Transgenic and Knock-out Mouse Core of UCSD is widely respected in the community and regarded as an essential resource for modern research. The availability of its services at substantially discounted rates will substantially improves the quality, quantity and creativity of the research, while also enhancina cost-effectiveness and efficiency.